Epithelial–mesenchymal transition plays a critical role in drug resistance of hepatocellular carcinoma cells to oxaliplatin
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Drug resistance is one characteristic of hepatocellular carcinoma (HCC) and can affect the prognosis of patients directly. To explore drug resistance well, we established an oxaliplatin (OXA)-resistant cell line Bel-7402/OXA by exposure to gradually increased concentration of OXA. Some biological characters, such as proliferation, migration, and invasion, were studied. Drug sensitivity and the mechanisms of drug resistance were also investigated. We found that the resistant index of Bel-7402/OXA was 8.3. In comparison with Bel-7402, the percentages of cells in S and G2/M phase were increased. The nature apoptosis rate and drug-after apoptosis rate were all decreased in Bel-7402/OXA, as compared to Bel-7402. Bel-7402/OXA acquired increased migration and invasion ability with epithelial–mesenchymal transition (EMT) phenotype. Knockdown of EMT transcription factor Snail could reverse EMT and sensitized Bel-7402/OXA cells to OXA. EMT was one mechanism of drug resistance and may be a novel target of treatment for drug resistance.
KeywordsHepatocellular carcinoma Oxaliplatin Drug resistance Epithelial–mesenchymal transition
This study was supported by the grants from the National Nature Science Foundation of China (No. 30770971, 81172470, 81070362, and 81372629).
Compliance with ethical standards
The manuscript has been performed with the approval of the institutional Ethics Committees of Xiangya Hospital, Central South University.
Conflicts of interest
The authors declare that they have no competing interests.
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